Sodium Hydroxide → HCID 69203295, compound

Participants

Reaction Steps

A mixture of N1-{4-[4-amino-1-(4-formylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide (Intermediate 2) (0.075 g, 0.14 mmol), (R)-(+)-3-pyrrolidinol (0.024 g, 0.27 mmol), and sodium triacetoxyborohydride (0.087 g, 0.41 mmol) in dichloroethane (1.4 mL) was shaken at room temperature for 3 days. Additional portions of (R)-(+)-3-pyrrolidinol (0.1 mL), and sodium triacetoxyborohydride (0.084 g, 0.40 mmol) were added and the reaction mixture was shaken for 16 h. 1N NaOH (1 mL) was added and the precipitate was collected by filtration and combined with the residue obtained from extraction of the water layer with one portion of dichloromethane (20 mL). The crude mixture was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 20-80% acetonitrile-0.05 M ammonium acetate over 25 min, 21 mL/min). The appropriate fraction was collected, concentrated, and lyophilized to afford N1-{4-[4-amino-1-(4-{[(3R)-3-hydroxytetrahydro-1H-1-pyrrolyl]methyl}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a white solid (0.034 g, 0.055 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.93 (1H, s), 8.34-8.37 (2H, m), 8.15-8.19 (2H, m), 7.98-8.01 (1H, m), 7.85 (1H, d, J=10.4 Hz), 7.75 (1H, d, J=8.0 Hz), 7.48-7.54 (2H, m), 7.44 (1H, s), 7.40 (1H, d, J=8.4 Hz), 4.70 (1H, bs), 4.22 (1H, s), 3.96 (3H, s), 3.63 (2H, s), 2.49-2.72 (3H, m), 2.13-2.41 (1H, m), 1.91-2.06 (1H, m), and 1.53-1.61 (1H, m); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 10.53 min. MS: MH+ 622.2.

Provenance & Evidence